Bronchiectasis · Neutrophil serine protease inhibition
Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis
| Design | Phase 3, randomised, double-blind, placebo-controlled trial with two doses |
|---|---|
| Treatment | Brensocatib 10 mg or 25 mg once daily |
| Control | Placebo |
| Population | 1721 patients with bronchiectasis, including 41 adolescents |
| Follow-up | 52 weeks |
| Primary endpoint | Annualised rate of pulmonary exacerbations |
| Result | Exacerbation rate 1.02 with brensocatib 10 mg, 1.04 with 25 mg and 1.29 with placebo — rate ratio 0.79 (95% CI 0.68 to 0.92, adjusted p=0.004) for 10 mg and 0.81 (0.69 to 0.94, adjusted p=0.005) for 25 mg. Hazard ratio for time to first exacerbation 0.81. FEV1 decline was less with the 25 mg dose than placebo. |
| Secondary endpoints | Time to first exacerbation, FEV1 decline, quality of life |
Among patients with bronchiectasis, once-daily treatment with brensocatib (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations than placebo, and the decline in FEV1 was less with the 25-mg dose of brensocatib than with placebo.
The trial authors, in the published abstract
The first positive phase 3 in a disease that had been managed entirely with borrowed treatments. Targeting neutrophil serine proteases rather than the organism is a genuinely new approach, and the FEV1 signal at the higher dose hints at disease modification rather than symptom control.
Chalmers JD, Burgel PR, Daley CL, et al. Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. N Engl J Med 2025 Apr 24;392(16):1569-1581.